Project Summary. South Africa (SA) is home to the largest number of people living HIV/AIDS (PLWH; 7.7 million) and one of the highest incidence rates of tuberculosis (TB) globally. Poor engagement in care contributes to HIV and TB morbidity and mortality in SA. Community health workers (CHWs) are frontline workers who play a central role in re-engaging patients who are lost to follow-up (LTFU) in TB/HIV care in SA. Despite existing CHW programs focused on re-engaging patients who are LTFU, people with depression, hazardous alcohol use, or other substance use (SU) are particularly susceptible to poor engagement in TB/HIV care and have a greater likelihood of being LTFU. Further, our pilot data shows that CHWs have high levels of stigma towards patients with depression, hazardous alcohol use, and other SU, which can further undermine engagement in TB/HIV care in this vulnerable population. Reducing CHW stigma towards depression and SU and providing CHWs skills to re-engage this population in care may be a unique opportunity to strengthen the TB/HIV care cascades and improve TB/HIV outcomes. Guided by the Link and Phelan stigma framework and the Situated Information Motivation Behavioral Skills Model of Care Initiation and Maintenance (sIMB-CIM), this proposal builds upon our prior work by developing and adapting a novel CHW training program to reduce CHW stigma towards depression and SU, and evaluating theoretically-driven implementation science outcomes and patient re-engagement in TB/HIV care. We are leveraging a robust, existing infrastructure of CHWs doing home visits with patients with TB/HIV co-infection who are LTFU, thus promoting the sustainability of the proposed model. We propose to (1) identify multi-level barriers and facilitators to implementing a CHW-oriented training to reduce stigma towards patients with depression and substance use to promote re-engagement in TB/HIV care by conducting semi-structured interviews with CHWs, providers, and patients with TB/HIV and depression and/or SU (n=30) and observational assessments of CHWs making home visits (n=10) to individuals with TB/HIV who were LTFU. Using this feedback, we will (2) adapt the proposed CHW training and implementation strategy and obtain feedback on the feasibility and acceptability from five CHWs and their patients (four patients each; n=20). We will then (3) evaluate the implementation and preliminary effectiveness of the adapted CHW training program to reduce CHW stigma towards depression and SU and promote re-engagement in TB/HIV care using a Type 2, hybrid effectiveness-implementation study guided by Proctor?s implementation model. We propose a stepped wedge design with six clinics (10 CHWs in each), to evaluate: 1) Feasibility, acceptability and fidelity of the CHW training (primary; implementation); 2) CHW stigma towards depression and SU among TB/HIV co- infected patients (primary; effectiveness); 3) Patient re-engagement in TB/HIV care over six months (secondary). This proposal is responsive to the FOA and NIMH priorities as an implementation science study to optimize the reach and impact of CHW programs to reduce barriers to TB/HIV care for patients with depression and SU.